The main emphasis of the proposed research is to investigate the cellular and synaptic mechanisms underlying the processes of light and dark adaptation. The major tenet is that the hard wiring anatomically defines the physical synapses, but synaptic efficacy is modified by neuromodulators, such as dopamine, to accommodate the shift from rod- to cone-vision during dark and light adaptation. Studies are proposed to examine the dependency of light, voltage, Ca2+ and dopamine (D2 receptors) on glutamate release by photoreceptors in a "reduced" retina preparation consisting of mostly photoreceptors, and by photoreceptor-derived synaptosomes. The effects of dopamine (D2) ligands on rod-cone coupling, as well as rod photovoltage and its flicker response will be examined with intracellular recordings and dye-coupling experiments. In addition, the kinetics of horizontal cell responses and coupling in the horizontal cell network will be studied during light/dark adaptation and during pharmacological manipulations. Recordings from isolated horizontal cells will be used to examine the modulatory effects of amino acid neurotransmitters on time- and voltage-dependent channels, and to assess the contribution each channel makes to sinusoidal modulation of the horizontal cell voltage within the physiological range. The role horizontal cells play in center-surround organization of ganglion cells and the variation of the surround strength as a consequence of light and dark adaptation will also be studied by passing current into horizontal cells while recording extracellular ganglion cell activity.